Regeneration of a functional and living tooth is a highly desirable approach for the replacement of a diseased or damaged tooth (1-3). Recent advances in dental stem cell biotechnology and cell-mediated murine tooth regeneration have encouraged researchers to explore the potential for regenerating living teeth with appropriate functional properties (4-6). It has been shown that murine teeth can be regenerated using many different stem cells to collaboratively form dental structures in vivo (4, 5, 7). In addition, dentin/pulp tissue and cementum/periodontal complex have been regenerated from human dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs), respectively, when transplanted into immunocompromised mice (8, 9). However, owing to the complexity of human tooth growth and development, the regeneration of a whole tooth structure, including enamel, dentin/pulp complex, and periodontal tissues, has not been possible by using currently available regenerative biotechnologies.
From a clinical perspective, the most important part of the tooth is the root which is required to support a (natural or artificial) crown; the crown alone cannot fulfill normal tooth function without a viable root. The spatially and temporally organized microenvironment of the tooth bud and its surrounding tissues permits growth and development of the crown and roots, resulting in formation and eruption of the tooth (10). Root development involves dentin formation, cementum generation, instruction of epithelium, and tooth eruption. Thus, the re-generation of a whole tooth is highly complicated and technically challenging. In contrast, the lesser challenging goal of replacing a damaged crown with a synthetic crown has been widely applied in dental clinics with excellent therapeutic outcomes (11).
However, despite the fact that dental implant therapies have achieved long-term success in the clinic for recovering tooth function, successful implantations require preexisting high-quality bone structures for supporting the implants (12, 13). Subjects who lack good bone structures are currently unable to benefit from such therapies. Hence, reconstruction of teeth in patients without adequate bone support would be a major advance.
Accordingly, there exits a need for improved therapeutic methods that can repair or replace damaged tooth in subjects who lack adequate bone support structures for tooth implants.